We have constructed a new time-scale, TT(IPTA16), based on observations of radio pulsars presented in the first data release from the International Pulsar Timing Array (IPTA). We used two analysis ...techniques with independent estimates of the noise models for the pulsar observations and different algorithms for obtaining the pulsar time-scale. The two analyses agree within the estimated uncertainties and both agree with TT(BIPM17), a post-corrected time-scale produced by the Bureau International des Poids et Mesures (BIPM). We show that both methods could detect significant errors in TT(BIPM17) if they were present. We estimate the stability of the atomic clocks from which TT(BIPM17) is derived using observations of four rubidium fountain clocks at the US Naval Observatory. Comparing the power spectrum of TT(IPTA16) with that of these fountain clocks suggests that pulsar-based time-scales are unlikely to contribute to the stability of the best time-scales over the next decade, but they will remain a valuable independent check on atomic time-scales. We also find that the stability of the pulsar-based time-scale is likely to be limited by our knowledge of solar-system dynamics, and that errors in TT(BIPM17) will not be a limiting factor for the primary goal of the IPTA, which is to search for the signatures of nano-Hertz gravitational waves.
A common metabolic alteration in the tumor microenvironment (TME) is lipid accumulation, a feature associated with immune dysfunction. Here, we examined how CD8+ tumor infiltrating lymphocytes (TILs) ...respond to lipids within the TME. We found elevated concentrations of several classes of lipids in the TME and accumulation of these in CD8+ TILs. Lipid accumulation was associated with increased expression of CD36, a scavenger receptor for oxidized lipids, on CD8+ TILs, which also correlated with progressive T cell dysfunction. Cd36−/− T cells retained effector functions in the TME, as compared to WT counterparts. Mechanistically, CD36 promoted uptake of oxidized low-density lipoproteins (OxLDL) into T cells, and this induced lipid peroxidation and downstream activation of p38 kinase. Inhibition of p38 restored effector T cell functions in vitro, and resolution of lipid peroxidation by overexpression of glutathione peroxidase 4 restored functionalities in CD8+ TILs in vivo. Thus, an oxidized lipid-CD36 axis promotes intratumoral CD8+ T cell dysfunction and serves as a therapeutic avenue for immunotherapies.
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•The tumor microenvironment is enriched with lipids and oxidized lipids•Dysfunctional CD8+ TILs increase CD36 expression and OxLDL uptake•OxLDL uptake via CD36 inhibits T cell effector functions through lipid peroxidation•GPX4 overexpression promotes CD8+ TIL functionality
Lipid accumulation is a common metabolic alteration in the tumor microenvironment. Xu et al. show that intratumoral CD8+ T cells adapt to increased lipid concentrations by increasing expression of the scavenger receptor CD36. This, in turn, leads to intracellular accumulation of oxidized lipid and T cell dysfunction downstream of lipid peroxidation.
The change in shape of atmospherically relevant organic particles is used to estimate the viscosity of the particle material without the need for removal from aerosol suspension. The dynamic shape ...factors chi of particles produced by alpha -pinene ozonolysis in a flow tube reactor, under conditions of particle coagulation, were measured while altering the relative humidity (RH) downstream of the flow tube. As relative humidity was increased, the results showed that chi could change from 1.27 to 1.02, corresponding to a transition from aspherical to nearly spherical shapes. The shape change could occur at elevated RH because the organic material had decreased viscosity and was therefore able to flow to form spherical shapes, as favored by the minimization of surface area. Numerical modeling was used to estimate the particle viscosity associated with this flow. Based on particle diameter and RH exposure time, the viscosity dropped from 10(8.7 plus or minus 2.0) to 10(7.0 plus or minus 2.0) Pa s (two sigma) for an increase in RH from < 5 to 58 % at 293 K. These results imply that the equilibration of the chemical composition of the particle phase with the gas phase can shift from hours at mid-range RH to days at low RH.
In hexaploid bread wheat ( Triticum aestivum L. em. Thell), ten members of the IWMMN ( International Wheat Microsatellites Mapping Network) collaborated in extending the microsatellite (SSR = simple ...sequence repeat) genetic map. Among a much larger number of microsatellite primer pairs developed as a part of the WMC ( Wheat Microsatellite Consortium), 58 out of 176 primer pairs tested were found to be polymorphic between the parents of the ITMI ( International Triticeae Mapping Initiative) mapping population W7984 x Opata 85 (ITMI pop). This population was used earlier for the construction of RFLP ( Restriction Fragment Length Polymorphism) maps in bread wheat (ITMI map). Using the ITMI pop and a framework map (having 266 anchor markers) prepared for this purpose, a total of 66 microsatellite loci were mapped, which were distributed on 20 of the 21 chromosomes (no marker on chromosome 6D). These 66 mapped microsatellite (SSR) loci add to the existing 384 microsatellite loci earlier mapped in bread wheat.
•A stress-path dependent axial stress-strain model of FRP-confined concrete is proposed.•The model considers stress-path history of confinement by using an adjusted active confined concrete ...stress.•The model was verified by 321 test results obtained by other researchers.
High-strength concrete (HSC) has higher strength-to-weight ratio and stiffness than normal-strength concrete (NSC). Therefore, the use of HSC can decrease the construction and demolition waste and embodied carbon content of structural members that enhances the urban sustainability. However, HSC is more brittle than NSC. To further push up the maximum concrete strength limit in practical construction, confining concrete by fibre-reinforced polymer (FRP) has been advocated to restore ductility. Compared with using hollow-steel tube as confinement, FRP has lighter weight, higher tensile strength, better corrosion resistance, and is more durable and flexible. Nevertheless, it is up to now a difficult task to predict accurately the uni-axial stress-strain behaviour of FRP-confined concrete since the effect of confining stress, concrete strength, hoop and axial strains are inter-related and need to be determined simultaneously. Herein, to better understand and simulate the behaviour of FRP-confined concrete, a stress-strain model has been developed, which consists of the following three main components: (1) A hoop strain equation elaborated from the authors’ previous study on steel-confined concrete columns for application to FRP-confined concrete; (2) A modified confined concrete model considering stress-path of confining stress (or history of hoop strain); (3) Interaction between FRP and concrete. The model was verified based on 321 test results obtained from the literature, the design application of the which to a broad range of FRP-confined concrete structures is thus ensured.
Summary
Background
The patatin‐like phospholipase 3 (PNPLA3) rs738409 gene polymorphism is an important genetic determinant of non‐alcoholic fatty liver disease (NAFLD). However, the associations ...between liver fat and metabolic traits in rs738409 G allele carriers and the allelic influence on this association have not been fully studied.
Aim
To investigate the influence of the PNPLA3 gene polymorphism on the association of liver fat with serum metabolic factors and carotid atherosclerosis.
Methods
Liver fat was measured by quantitative ultrasound in 4300 subjects in the Shanghai Changfeng community and analysed for its association with obesity and metabolic factors in individuals with the PNPLA3 CC, CG and GG genotypes.
Results
Non‐alcoholic fatty liver disease occurred in 37.9% and 28.8% of the subjects with the GG and CC genotypes respectively (P < 0.001). Liver fat was significantly associated with body mass index, waist circumference, serum triglycerides, high‐density lipoprotein cholesterol, fasting blood glucose and insulin in the PNPLA3 rs738409 G allele carriers (P < 0.001). Compared with the CC homozygotes, the GG homozygotes presented higher liver fat and liver fibrosis scores despite their better metabolic status (comparison of regression line slopes, P < 0.05). An increase in liver fat was accompanied by a significant increase in the average and maximum carotid intima‐media thickness in subjects with the PNPLA3 CC genotype but not in those with the GG genotype.
Conclusions
PNPLA3 rs738409 G allele carriers were found to be more susceptible to the metabolic‐related hepatic steatosis, and developed NAFLD and liver fibrosis despite presenting relatively better metabolic statuses and lower risks for carotid atherosclerosis.
Physical and cognitive exercise may prevent or delay dementia in later life but the neural mechanisms underlying these therapeutic benefits are largely unknown. We examined structural and functional ...magnetic resonance imaging (MRI) brain changes after 6 months of progressive resistance training (PRT), computerized cognitive training (CCT) or combined intervention. A total of 100 older individuals (68 females, average age=70.1, s.d.±6.7, 55-87 years) with dementia prodrome mild cognitive impairment were recruited in the SMART (Study of Mental Activity and Resistance Training) Trial. Participants were randomly assigned into four intervention groups: PRT+CCT, PRT+SHAM CCT, CCT+SHAM PRT and double SHAM. Multimodal MRI was conducted at baseline and at 6 months of follow-up (immediately after training) to measure structural and spontaneous functional changes in the brain, with a focus on the hippocampus and posterior cingulate regions. Participants' cognitive changes were also assessed before and after training. We found that PRT but not CCT significantly improved global cognition (F(90)=4.1, P<0.05) as well as expanded gray matter in the posterior cingulate (P
<0.05), and these changes were related to each other (r=0.25, P=0.03). PRT also reversed progression of white matter hyperintensities, a biomarker of cerebrovascular disease, in several brain areas. In contrast, CCT but not PRT attenuated decline in overall memory performance (F(90)=5.7, P<0.02), mediated by enhanced functional connectivity between the hippocampus and superior frontal cortex. Our findings indicate that physical and cognitive training depend on discrete neuronal mechanisms for their therapeutic efficacy, information that may help develop targeted lifestyle-based preventative strategies.
Southern rice black‐streaked dwarf virus (SRBSDV) was first reported in southern China in 2001 and causes a striking disease on rice and maize that leads to serious yield losses in several East Asian ...countries, such as China, Vietnam and Japan. A large research effort has been directed to understanding the virus and controlling the disease. Its geographic distribution, disease cycle via its insect vector, genome organization, relationship with host plants, and epidemiology are summarized in this review and the important role played by the vector, the white‐backed planthopper (Sogatella furcifera), is emphasized. Countermeasures to control the disease that have been developed and applied include molecular detection for precise forecasting, chemical, physical, and ecological pest management. There is widespread insecticide resistance in the vector population but it is hoped that current efforts to develop rice cultivars resistant to the virus will eventually provide effective and cost‐effective control.
Molecular dynamics simulations were used to study deformation mechanisms during uniaxial tensile deformation of an amorphous polyethylene polymer. The stress-strain behavior comprised elastic, yield, ...strain softening and strain hardening regions that were qualitatively in agreement with previous simulations and experimental results. The chain lengths, number of chains, strain rate and temperature dependence of the stress-strain behavior was investigated. The energy contributions from the united atom potential were calculated as a function of strain to help elucidate the inherent deformation mechanisms within the elastic, yield, and strain hardening regions. The results of examining the partitioning of energy show that the elastic and yield regions were mainly dominated by interchain non-bonded interactions whereas strain hardening regions were mainly dominated by intra-chain dihedral motion of polyethylene. Additional results show how internal mechanisms associated with bond length, bond angle, dihedral distributions, change of free volume and chain entanglements evolve with increasing deformation.
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The limited potassium‐ion intercalation capacity of graphite hampers development of potassium‐ion batteries (PIB). Edge‐nitrogen doping is an effective approach to enhance K‐ion storage in ...carbonaceous materials. One shortcoming is the lack of precise control over producing the edge‐nitrogen configuration. Here, a molecular‐scale copolymer pyrolysis strategy is used to precisely control edge‐nitrogen doping in carbonaceous materials. This process results in defect‐rich, edge‐nitrogen doped carbons (ENDC) with a high nitrogen‐doping level (up to 10.5 at %) and a high edge‐nitrogen ratio (87.6 %). The optimized ENDC exhibits a high reversible capacity of 423 mAh g−1, a high initial Coulombic efficiency of 65 %, superior rate capability, and long cycle life (93.8 % retention after three months). This strategy can be extended to design other edge‐heteroatom‐rich carbons through pyrolysis of copolymers for efficient storage of various mobile ions.
Edge contributes more: A molecular scale edge‐nitrogen doping method is developed for synthesizing highly edge‐nitrogen‐doped carbons. This doped carbon shows a high nitrogen doping ratio of 10.5 at % (87.6 % edge‐nitrogen ratio), and a high, reversible, stable K‐ion storage capacity of 423 mAh g−1.
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